The objectives of the proposed research are to determine whether a viral agent can be implicated in the etiology of Paget's disease of bone. Recent electron microscopic studies of bone cells in Paget's disease have revealed the presence of characteristic nuclear inclusions in the osteoclasts. These inclusions most closely resemble viral nucleocapsids of the paramyxovirus type. These have also been found in the cells cultured from Paget's disease bone. The clinical course of the disease is consistent with a slow virus disease. Bone has been obtained from patients undergoing orthopaedic surgery to correct disabilities of the disease. Specific immunofluorescent and immunoperoxidase methods have been used to search for a virus in bone and in cells derived from bone. Positive staining of osteoclasts in bone from three different patients using antibodies grown in rabbit and in guinea pig has been obtained for respiratory syncytial virus, with the immunoperoxidase method. Positive immuofluorescent staining of osteoclasts in bone has also been obtained for the same virus but autofluorescence not completely quenched by Evans blue requires the use of rhodamine conjugate antibody for confirmation. Also specific immunofluorescene with antisera to respiratory syncytial virus was obtained in early passages of cells from four different patients. These results require confirmatory testing which is continuing. Cells from Paget's patients have been injected into Nude (nu/nu) mice. After 8 1/2 months a few animals have been sacrificed. The brain of one of these mice contained cells with nuclear inclusions measuring approximately 16 nm. and morphologically identical to those of Paget's patients. These results are suggestive and further studies are continuing.